The broad objective is to understand the relationship between cellular metabolism and (a) membrane ionic permeabilities, (b) transmembrane ionic gradients and (c) subcellular compartmentation of various ions. Mitochondrial transport of Naion and Ca to the 2nd power ion ions via neutral exchange with protons will be emphasized and the influence of these exchanges upon mitochondrial pH gradients and distribution of anionic metabolites between mitochondrial and cytoplasmic compartments. The possible interplay between mitochondrial Ca to the 2nd power ion and Na ion transport will be studied to determine whether the translocation of Na ion may regulate the levels of Ca ion within the cytosol. The experimental approach will involve comparative studies of isolated cells, mitochondria, submitochondrial particles and model membrane systems to elucidate selected permeabilities and regulatory influences that may operate in vivo. The influence of certain hormones upon plasma membrane permeability (e.g. glucagon, epinephrine, parathyroid hormone, etc.) and metabolism will form part of the above studies to establish the degree to which intracellular ions (particularly Ca to the 2nd power ion) determine the cellular response to these agents. The studies outlined will be applied principally to isolated liver cells and corresponding subcellular components for comparison to results obtained with a selected variety of tumor cells to determine the extent to which the indicated ions and their translocation between compartments affects the oxidative and glycolytic metabolism of tumor cells together with relevant hormonal influences upon these processes in normal and neoplastic cells.